Expression of mRNA for luteinizing hormone-releasing hormone receptors and epidermal growth factor receptors in human cancer cell lines.
Conventional chemotherapy produces varying degrees of response in patients with many advanced cancers and has significant side effects. Receptors for luteinizing hormone-releasing hormone (LH-RH) are present in a high percentage of human ovarian, prostatic, breast and endometrial tumors and targeted chemotherapy based on cytotoxic analogs of LH-RH might yield better results. The present study was undertaken to determine whether human cancer cell lines express mRNA for LH-RH receptors and epidermal growth factor (EGF) receptors. Using radioligand binding studies, we showed the presence of high-affinity binding sites for LH-RH and EGF in the membranes of human ovarian, prostatic, breast and endometrial cancer cell lines as well as in the JAR choriocarcinoma cell line. The expression of the mRNA for LH-RH receptors and EGF receptors in these cell lines was demonstrated by RT-PCR using specific primers and by subsequent Southern blot analysis. The PCR products obtained were of the expected size, 319 bp for LH-RH receptors and 400 bp for EGF receptors. These findings support the view that cytotoxic analogs of LH-RH could be used for targeted chemotherapy of these cancers. Moreover, the results suggest that these human cancer cell lines might have local regulatory systems for their proliferation based on LH-RH and EGF. Further investigations are required to elucidate the signal transduction pathways involved in the effects of cytotoxic LH-RH analogs on human tumors.
Lamharzi
N
N
Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, New Orleans, LA 70146, USA.
Halmos
G
G
Armatis
P
P
Schally
A V
AV
D015139:Blotting, Southern; D001943:Breast Neoplasms; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002822:Choriocarcinoma; D016889:Endometrial Neoplasms; D066246:ErbB Receptors / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D008297:Male; D010051:Ovarian Neoplasms; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011471:Prostatic Neoplasms; D012333:RNA, Messenger / Q000096:biosynthesis; D011869:Radioligand Assay; D011966:Receptors, LHRH / Q000096:biosynthesis*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms
D012333:RNA, Messenger; D011966:Receptors, LHRH; D066246:ErbB Receptors